Cancer and Other Mortality Risks in a Cohort of U.S. Radiologic Technologists In 1982, the Radiation Epidemiology Branch (REB), in collaboration with the University of Minnesota, initiated a nationwide cohort study of all cancer incidence and mortality among 146,022 U. S. radiologic technologists. The cohort is 73% female, offering a rare opportunity to study effects of occupational protracted low- to moderate-dose radiation exposure on breast and thyroid cancer, the two most sensitive organ sites for radiation carcinogenesis in women. All other cancer and non-cancer serious disease outcomes are also being evaluated in relation to protracted low-to-moderate dose exposures. Mutational analysis of the ATM genes revealed that mutations in these genes are unlikely to account for a significant fraction of inherited breast cancer but a few low-frequency polymorphisms may increase breast cancer risk. Nearly 74,000 of 102,000 (72%) known living first or second survey responders participated in the third comprehensive survey of this cohort. We published our first semi-quantitative radiation risk assessment for breast cancer. Studies of breast cancer and genetic polymorphisms in several gene pathways (e.g. ATM, double strand break repair, base excision repair, apoptosis) were completed and manuscripts published. Venipuncture blood samples were collected from another 756 breast cancer cases identified on the third survey, and a pilot study of DNA fingerprick blood sample collection by mail was launched. Additionally, we completed development of the Version-4.0 dosimetry system. Corroboration of 152 lifetime occupational and medical radiation dose estimates using individual FISH measurements gives us confidence to use the Version 4.0 dose estimates to conduct dose-response analyses and proceed with publication. Cancer Mortality in Russian Nuclear Workers Exposed to Plutonium and Protracted External Radiation A cohort of 26,000 Mayak nuclear facility workers (in the Russian Federation) is being studied because they comprise a unique occupational group for protracted exposure to external occupational radiation at high doses and exposure to plutonium. Dose-response relationships for exposure to external radiation were demonstrated for mortality from leukemia; lung cancer, liver cancer and bone cancer (analyzed as a single category); and all solid cancers other than lung cancer, bone cancer and liver cancer. Patterns of risk by sex, age at exposure and time since exposure were generally similar to those observed in A-bomb survivors. Mortality analyses have also clearly demonstrated that internal exposure to plutonium results in excess risks for lung cancer, liver cancer and bone cancer, the sites receiving the highest doses from plutonium. Dose-response analyses of lung cancer mortality indicated significant associations for both internal dose to the lung from plutonium and external dose (p less than .001). These relationships were adequately described by linear functions, and both the excess relative risk (ERR) and excess absolute risk (EAR) were found to depend strongly on gender and attained age. Similar analyses evaluating risks of liver cancer and bone cancer mortality also indicate significant dose-response relationships. Germline Genetic Variation And Risk Of Chromosome Aberrations Among Mayak Nuclear Workers REB is collaborating with the Southern Urals Biophysics Institute and Columbia University to elucidate the contribution of germline genetic variation to the frequency of chromosomal aberrations in a cohort of workers at the Mayak nuclear weapons facility. These workers were exposed to gamma and plutonium occupational radiation. Leukemia and Other Cancer Incidence in Chornobyl Clean-Up Workers NCI has conducted several studies of Chornobyl clean-up workers. All cancer incidence through 1998 was evaluated in two cohorts, comprising 10,000 clean-up workers, from Estonia and Latvia, who were sent to Chornobyl (Ukraine) following the reactor accident in 1986. Leukemia did not occur significantly more often than expected based on incident rates for the general population. Thyroid cancer incidence was increased, but this appeared to have been due, at least in part, to thyroid screening. The study is being extended to include a cohort of 7,000 clean-up workers from Lithuania and additional years of follow-up. In addition NCI has recently completed a "nested" case-control study of leukemia and other hematologic diseases among the approximately 110,000 Chornobyl clean-up workers in Ukraine and is continuing to accrue cases through record linkage with the Ukranian National Cancer Registry. (Phase II) Incidence of Breast Cancer and Other Cancers and Chromosome Aberrations in Flight Personnel A cancer incidence study of N=9,631 female flight attendants is underway in collaboration with investigators at the National Institute of Occupational Safety and Health to determine whether these workers are at increased risk of breast cancer or other cancers due to cosmic radiation exposure. Surveys from living or proxy respondents have been collected from 6,341 female flight attendants. Confirmation of cancer diagnoses from death certificates or medical records is ongoing. Data cleaning and preparation of analysis files are also ongoing activities. A study of markers of cosmic radiation exposure and effect among flight crew A biodosimetry study to assess cosmic radiation exposure aimed to compare the induction and persistence of chromosome aberrations by fluorescence in situ hybridization (FISH) among 83 pilots and 51 university faculty with minimal flying experience. We found that the mean frequency of translocations did not differ between the airline pilots and a comparison group of university faculty, however there was a significant increasing trend among the pilots between number of years flying commercial aircraft and translocation frequency. Cosmic radiation doses based on pilot logbooks and airline company records are being calculated so that further analysis by dose can be performed. Fluorescence in situ Hybridization (FISH) Chromosomal Aberration Analysis among US Radiologic Technologists Measurement of chromosome translocations in peripheral blood lymphocytes has been used to quantify prior exposure to ionizing radiation, including for workers exposed to low, chronic doses, such as our cohort of US Radiologic Technologists. We assessed translocation frequencies in 152 technologists to substantiate our cohort-wide ionizing radiation dose estimates. Despite uncertainty in the estimates of occupational red bone marrow absorbed doses, we found good general agreement between the doses and translocation frequencies, lending support to the credibility of the dose assessment for this large cohort of U.S. radiologic technologists. In addition we found that radiation exposure from prersonal diagnostic x-ray procedures was positively associated with translocation frequencies after adjustment for age and occupational radiation doses.